Member Info for RayPointer

CAR-T still needs an antigen to target as does TCR.
So maybe, if and when the Moditope targets are proven, engineering CAR-T receptors for Moditope targets may be a possibility. BionTech are into CAR-T as well as TCR.
If this does happen, I suspect it is well into the future.
But, who knows, CAR-T receptors with Moditope targets could prove ultimately to be the very best treatment, albeit probably the most expensive.

I wasn't aware that Scancell were in collaboration or trial with Car-T.

Now there as a man ahead of his time!

It's all about Lindy

https://angelnumber.org/313-angel-number-meaning-and-symbolism/

The number 313, as a blend of all these energies, signifies creativity, abilities, gifts, talents, spontaneity, optimism, joy, happiness, individuality, increase, expansion, progress, moving forward, success, achievements, determination, self – expression and open – mindedness.

Even more sporting diversions the following weekend with Burnley having friendlies against Port Vale and Crewe.

Cars
But maybe this is a trader buying on dips and selling on peaks. Who knows?
I certainly think we will see bouts of profit taking from time to time.
ATB

On one of the placings wasn't it the case that a number of IIs bought in small non notifiable amounts. From memory I think there were 18 IIs but I might be wrong. So Woodford could have bought a small amount (by II standards).

A new verb in the English language:
to diggle
To buy undervalued shares close to the bottom.

Also a noun
the act of diggling.

So Martin Diggle diggled a diggle.

Thanks for that nom.
2009 was pre moditope but I believe protein unfolding is relevant to Moditope.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4922435/

"Damaged cells activate PADI enzymes, which convert arginines to citrullines, thereby, changing charge and leading to unfolding of proteins."

I am guessing here that the unfolding of the proteins leads to more of the citrullinated epitopes to be made vunerable to attack by the immune system

The reference to PADI enzymes is also interesting. There is a company called Padlock bought out by BMS that is working on blocking the PAD enzymes to stop the progression of autoimmune diseases.

https://www.healio.com/rheumatology/rheumatoid-arthritis/news/online/%7Bc2ccd7d5-386c-4ac4-b615-8e3ced809d7e%7D/bristol-myers-squibb-to-acquire-padlock-therapeutics-with-ra-autoimmune-pipeline

"PADs are an autoantigen-producing family of enzymes that may actively work in the development and progression of RA and other autoimmune diseases, and their inhibition may alter disease progression."

So, 2 companies
1 trying to stop citrullination
1 trying to exploit citrullination

C7, how about installing an electrically operated revolving door!

You are most welcome Ruck.
I hope it increases your understanding.
I just find it all very fascinating (and I think Ugur Sahin does too)

It is also worth pointing out the chemistry behind citrullination so give the citrullination article a second look

https://en.wikipedia.org/wiki/Citrullination

So essentially citrullination is the replacement of NH (Nitrogen and Hydrogen bound together) with an Oxygen atom.
A tiny change in the large molecular structure that is a protein.
But the crucial point it that it takes place in stressed cancer cells and not in healthy cells.

So the next thing Lindy had to do was find the specific epitopes (targets) that exhibit citrullination.
By February of last year she had found 37 such targets of which 7 had been investigated and all showing a tumour response
(a cancer research scientist's wet dream).

For Modi1 she decided on 3 epitopes, 2 on a protein called Vimentin and 1 on a protein called Enolase.
Presumably her choice was based on how commomly the chosen epitopes are expressed in a range of cancers.

So, in summary, the vital elements to understand are:

Protein - amino acids strings
Epitope - part of the antigen that components of the immune system can bind to
(a short string of amino acids in this case)
Arginine - the particular amino acid targeted by Modi1 (but in its cictullinated form called Citrulline)
Autophagy - caused by stress
Citrullination - a by product of autophagy
Vimentim and Enolase - the proteins whose citrullinated epitopes modi1 targets

I hope this helps, and I hope my interpretation is correct, but it only tells part of the story.
Next, once I get the chance, it is worth exploring exactly how Lindy exploits these 3 targets.

The immunotherapy approach to fighting cancer often involves blocking off certain proteins which help the cancer avoid an immune attack
or alternatively giving a hand to the immune system in its battle via a vaccine that primes the immune system to mount a successful attack.

The former approach is used in CIs such as Keytruda but it is the latter approach that Lindy has chosen.

The most important aspect of Lindy's approach is to first choose a target or targets on the surface of the cancer that is there to attack.
The target should be something that is expressed on cancer cells but not on healthy cells. Also it helps enormously if the target is expressed in large quantities on the surface of the tumour.

IMO, Lindy studied autoimmune diseases such as rheumatoid arthritis to try and identify viable targets. After all, this is where the immune system goes wrong in that it attacks healthy cells.
So, a link was already known between rheumatoid arthritis and a process called citrullination - specifically on proteins

https://en.wikipedia.org/wiki/Citrullination#Autoimmune_diseases

Before going further let's have a closer look at what a protein is.
Proteins comprise long chains of amino acids, the acids being joined together with a specific type of chemical bond called a peptide bond.
A target on the protein is called an epitope and is typically about 6 amino acids in length and I think in this context it can also be called a peptide.

https://en.wikipedia.org/wiki/Protein
https://en.wikipedia.org/wiki/Epitope
https://en.wikipedia.org/wiki/Amino_acid

So, if Lindy were to create a vaccine to attack an epitope in its normal state it would possibly have dire consequences as it would attach healthy cells as well as cancer cells.
This is the reason why clinical trials are preceded by a huge document concerning toxicity of the product to be trialled.

So, Lindy studied citrullination in cancer cells as a possible mode of attack.
Stress is the key since this leads to a process called autophagy which in turn leads to citrullination.
Listen to Lindy talking about this sequence in the calculus presentation of last year.
She explains it much better than I could (about 15:55 in)

https://www.youtube.com/watch?v=CXyPYib5JWc

Here's another explanation of autophagy. It appears that the stressed cells consume some of
their own proteins in order to survive.

https://www.news-medical.net/life-sciences/What-is-Autophagy.aspx

Here's another article that debates whether autophagy is a good or bad thing for our fight against cancer.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4349374/

But for Moditope it is definitely a good thing in that it leads to citrullination.

OK it may be towards the end of the week since l am very busy at the moment, but I promise I will set the ball rolling with a post on the moditope targets.

C7, how are you M8?
Great to see you still posting after your bad news over the weekend.
Something I have been thinking of doing is to pull together all I know about moditope and try to present it in a coherent way.
Do you think this would help? I can't promise how long this would take but it may spark some discussion on the merits of Scancell's approach and hopefully lead to a better general understanding for the science.

Great news C7.
You seem to be able to pick the right treatment LOL.

On the subject of individualised mutations, this is exactly what the Genetech/Biontech collaboration is aiming at.
Identify the individual mutations and create a vaccine to target these mutations. Potentially, a different vaccine for each patient.

Our own Lindy does not rate this approach
a) tumour outgrowths often do not express the same mutations
b) It is expensive
c) She reckons it will only work in 10-20% of patients
Also, I believe this trial is in combo with a CI - probably the Roche CI.

One of the facets of Moditope that Lindy emphasises is that citrullinated peptides are very commonly expressed in most patients and in a wide range of cancers. Modi1 has 3 such targets, so having 3 it further increases the chances of getting a response. Stress in the cancer cells is the key and causes the expression of the peptides via autophagy

So
Stress (very common in cancer cells) -> Autophagy->Citrullination

Also it would appear that once those lovely CD4 killers attach to tumour cells, it sets off a chain reaction that causes more stress. Meanwhile clonal expansion is being triggered close to the tumour creating more of those CD4 killers.
So initially only low penetration of the tumour environment is required by the original CD4 killers.

If it works and my interpretation is correct, it seems a very clever solution to me.

I've just found pictures of scancell climbing the cliff

https://www.mirror.co.uk/news/uk-news/dont-look-down-daredevil-free-climber-747420

I agree C7. They will just respond with vague statements about collaborations and not give much away.

But don't underestimate how long it takes for a collaboration to come to fruition. There will be breakthroughs, some expected and some unexpected, along the way that need to be thoroughly investigated. There will be specific problems to overcome also.

I thought it was a good discussion yesterday with opposing views aired and without any falling out.

The other possible factor is the Genentech/BionTech collaboration on the neo-antigen trial and its timescales.
"How does this compare to Moditope?" BionTech may be asking.
BionTech could be hedging their bets by waiting for data from both this trial and the Modi1 trial.

And then you could possibly bring Genetech's interest in moditope into the mix. We know they have an interest in moditope from Ira Mellman's inclusion in Lindy's GC team.

All pure speculation at this stage.

You are right TF "we just don't know".
There are a number of factors affecting the timing of the deal, the most important of which is the conclusion of the scientific work BionTech and Scancell are conducting.

Other factors then include:

a) the length of time it takes to conclude a deal
b) whether BionTech want to wait for the first clinical indication that Moditope does work and how well it works (the Modi1 trial is due to start early next ear)
c) whether the BionTech IPO is getting in the way
d) The fine detail of the collaboration - for instance how long after concluding the scientific work does BionTech have first dibs on Moditope TCR?

Ugur Sahin and his view of moditope is the key. Has anyone asked him LOL